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https://www.readbyqxmd.com/read/28440423/upregulated-microrna-429-inhibits-the-migration-of-hcc-cells-by-targeting-traf6-through-the-nf-%C3%AE%C2%BAb-pathway
#1
Peng Wang, Jia Cao, Shihai Liu, Huazheng Pan, Xiangping Liu, Aihua Sui, Liping Wang, Ruyong Yao, Zimin Liu, Jun Liang
Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. however, its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that miR-429 was significantly downregulated in HCC tissue samples and cell lines. Upregulation of miR-429 markedly suppressed proliferation and migration of HCC cells. Moreover, we identified TRAF6 as a direct target of miR-429. Downregulation of TRAF6 partially attenuated the oncogenic effect of anti‑miR-429 on HCC cells...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28437727/new-inter-correlated-genes-targeted-by-diatom-derived-polyunsaturated-aldehydes-in-the-sea-urchin-paracentrotus-lividus
#2
Nadia Ruocco, Anna Maria Fedele, Susan Costantini, Giovanna Romano, Adrianna Ianora, Maria Costantini
The marine environment is continually subjected to the action of stressors (including natural toxins), which represent a constant danger for benthic communities. In the present work using network analysis we identified ten genes on the basis of associated functions (FOXA, FoxG, GFI-1, nodal, JNK, OneCut/Hnf6, TAK1, tcf4, TCF7, VEGF) in the sea urchin Paracentrotus lividus, having key roles in different processes, such as embryonic development and asymmetry, cell fate specification, cell differentiation and morphogenesis, and skeletogenesis...
April 21, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28430599/tak1-inhibitor-5z-7-oxozeaenol-sensitizes-cervical-cancer-to-doxorubicin-induced-apoptosis
#3
Shan Guan, Jiaxiong Lu, Yanling Zhao, Sarah E Woodfield, Huiyuan Zhang, Xin Xu, Yang Yu, Jing Zhao, Shayahati Bieerkehazhi, Haoqian Liang, Jianhua Yang, Fuchun Zhang, Surong Sun
Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress, is required for tumor cell viability and survival. Herein, we examined whether TAK1 inhibition is a potential therapeutic strategy for treating cervical cancer. We found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of Dox in a panel of cervical cancer cell lines...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424289/disruption-of-mda5-mediated-innate-immune-responses-by-the-3c-proteins-of-coxsackievirus-a16-coxsackievirus-a6-and-enterovirus-d68
#4
Yajuan Rui, Jiaming Su, Hong Wang, Junliang Chang, Shaohua Wang, Wenwen Zheng, Yong Cai, Wei Wei, James T Gordy, Richard Markham, Wei Kong, Wenyan Zhang, Xiao-Fang Yu
Coxsackievirus A16 (CV-A16), A6 (CV-A6), and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C(pro) proteins from CV-A16, CV-A6, and EV-D68 bind MDA5 and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I IFN signaling in the RLR pathway was blocked by CV-A16, CV-A6, and EV-D68 3C(pro) Furthermore, CV-A16, CV-A6, and EV-D68 3C(pro) all cleave TAK1, resulting in inhibition of NF-κB activation, a host response also critical for toll-like receptor (TLR) mediated signaling...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28416436/molecular-cloning-of-chicken-interleukin-17b-which-induces-proinflammatory-cytokines-through-activation-of-the-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Cong Thanh Hoang, Yeojin Hong, Anh Duc Truong, Janggeun Lee, Kyungbaek Lee, Yeong Ho Hong
Interleukin (IL)-17B is a little known member of the IL-17 cytokine family, which plays an important role in immunity by regulating the expression of proinflammatory cytokines. In this study, we determined the coding sequence and biological functions of a novel chicken IL-17B (chIL-17B). The full-length chIL-17B coding sequence includes 567 nucleotides encoding 188 amino acids, which was identified in small intestinal epithelial cells. The chIL-17B protein shares 96.48% amino acid sequence identity with turkey, 92...
April 14, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28415764/inhibitor-of-tec-kinase-lfm-a13-decreases-pro-inflammatory-mediators-production-in-lps-stimulated-raw264-7-macrophages-via-nf-%C3%AE%C2%BAb-pathway
#6
Fei Wang, Wei Zhang, Chao Wang, Xu Fang, Hao Cheng, Sheng Liu, Xu-Lin Chen
Tec kinase, a prototypical member of the Tec tyrosine kinases family, was shown to mainly govern lymphocyte proliferation. In the present study, we investigated the role of Tec kinase in acute inflammatory response in lipopolysaccharide (LPS) challenge. First, we demonstrate that Tec kinase activity was observed in RAW264.7 macrophages exposed to LPS. Tec and phosphorylated Tec expression were upregulated in a dose- and time-dependent manner after LPS stimulation. LPS increased monocyte chemotactic protein (MCP)-1 secretion and intercellular adhesion molecule (ICAM)-1 expression, and increasing mRNA expression was consistently observed...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410990/tyrosine-kinase-syk-licenses-myd88-adaptor-protein-to-instigate-il-1%C3%AE-mediated-inflammatory-disease
#7
Prajwal Gurung, Gaofeng Fan, John R Lukens, Peter Vogel, Nicholas K Tonks, Thirumala-Devi Kanneganti
Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6(spin) mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6(spin) mice. We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6(spin) mice. Our studies further demonstrated that SHP1 encoded by Ptpn6 binds and suppresses SYK activation to inhibit MyD88 phosphorylation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28404732/roles-of-the-traf6-and-pellino-e3-ligases-in-myd88-and-rankl-signaling
#8
Sam Strickson, Christoph H Emmerich, Eddy T H Goh, Jiazhen Zhang, Ian R Kelsall, Thomas Macartney, C James Hastie, Axel Knebel, Mark Peggie, Francesco Marchesi, J Simon C Arthur, Philip Cohen
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells...
April 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28389629/inhibition-of-p70-s6-kinase-s6k1-activity-by-a77-1726-the-active-metabolite-of-leflunomide-induces-autophagy-through-tak1-mediated-ampk-and-jnk-activation
#9
Xiulong Xu, Jing Sun, Ruilong Song, Michelle E Doscas, Ashley J Williamson, Jingsong Zhou, Jun Sun, Xinan Jiao, Xiufan Liu, Yi Li
mTOR activation suppresses autophagy by phosphorylating ULK1 at S757 and suppressing its enzymatic activity. Here we report that feedback activation of mTOR in the PI-3 kinase pathway by two p70 S6 kinase (S6K1) inhibitors (PF-4708671 and A77 1726, the active metabolite of an immunosuppressive drug leflunomide) or by S6K1 knockdown did not suppress but rather induced autophagy. Suppression of S6K1 activity led to the phosphorylation and activation of AMPK, which then phosphorylated ULK1 at S555. While mTOR feedback activation led to increased phosphorylation of ULK1 at S757, this modification did not the disrupt ULK1-AMPK interaction nor dampen ULK1 S555 phosphorylation and the induction of autophagy...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386937/a-recognizable-systemic-connective-tissue-disorder-with-polyvalvular-heart-dystrophy-and-dysmorphism-associated-with-tab2-mutations
#10
Marco Ritelli, Silvia Morlino, Edoardo Giacopuzzi, Laura Bernardini, Barbara Torres, Graziano Santoro, Viola Ravasio, Nicola Chiarelli, Daniela D'Angelantonio, Antonio Novelli, Paola Grammatico, Marina Colombi, Marco Castori
Deletions encompassing TAK1-binding protein 2 (TAB2) associate with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism...
April 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28386315/protective-benefits-of-amp-activated-protein-kinase-in-hepatic-ischemia-reperfusion-injury
#11
REVIEW
Min Zhang, Dan Yang, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Li Zhang
Hepatic ischemia-reperfusion injury (HIRI) is a major cause of hepatic failure and death after liver trauma, haemorrhagic shock, resection surgery and liver transplantation. AMP-activated protein kinase (AMPK) is an energy sensitive kinase that plays crucial roles in the regulation of metabolic homeostasis. In HIRI, ischemia induces the decline of ATP and the increased ratio of AMP/ATP, which promotes the phosphorylation and activation of AMPK. Three AMPK kinases, liver kinase B1 (LKB1), Ca(2+)/calmodulin-depedent protein kinase kinase β (CaMKKβ) and TGF-β-activated kinase-1 (TAK1), are main upstream kinases for the phosphorylation of AMPK...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28380356/necroptosis-execution-is-mediated-by-plasma-membrane-nanopores-independent-of-calcium
#12
Uris Ros, Aida Peña-Blanco, Kay Hänggi, Ulrich Kunzendorf, Stefan Krautwald, W Wei-Lynn Wong, Ana J García-Sáez
Necroptosis is a form of regulated necrosis that results in cell death and content release after plasma membrane permeabilization. However, little is known about the molecular events responsible for the disruption of the plasma membrane. Here, we find that early increase in cytosolic calcium in TNF-induced necroptosis is mediated by treatment with a Smac mimetic via the TNF/RIP1/TAK1 survival pathway. This does not require the activation of the necrosome and is dispensable for necroptosis. Necroptosis induced by the activation of TLR3/4 pathways does not trigger early calcium flux...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28377500/innate-immune-signaling-in-drosophila-is-regulated-by-tgf%C3%AE-activated-kinase-tak1-triggered-ubiquitin-editing
#13
Li Chen, Nicholas Paquette, Shahan Mamoor, Florentina Rus, Anubhab Nandy, John Leszyk, Scott A Shaffer, Neal Silverman
Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila, the Imd pathway detects gram-negative bacterial infections through recognition of DAP-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide (AMP) gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and K63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear...
April 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28373409/activation-of-tgf-%C3%AE-activated-kinase-1-promotes-colon-mucosal-pathogenesis-in-inflammatory-bowel-disease
#14
Zhiwei Liu, Fansheng Kong, Jefferson E Vallance, Eleana Harmel-Laws, Surya Amarachintha, Kris A Steinbrecher, Michael J Rosen, Sandip Bhattacharyya
The etiology and mechanisms for inflammatory bowel disease (IBD) are incompletely known. Determination of new, clinically important mechanisms for intestinal inflammation is imperative for developing effective therapies to treat IBD We sought to define a widespread mechanism for colon mucosal inflammation via the activation of TGF-β activated Kinase 1 (TAK1), a central regulator of cellular inflammatory actions. Activation of TAK1 and the downstream inflammatory signaling mediators was determined in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD) as well as in DSS-induced and spontaneous IBD in mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28368397/molecular-impact-of-selective-nfkb1-and-nfkb2-signaling-on-dlbcl-phenotype
#15
X Guo, J L Koff, A B Moffitt, M Cinar, S Ramachandiran, Z Chen, J M Switchenko, M Mosunjac, S G Neill, K P Mann, M Bagirov, Y Du, Y Natkunam, H J Khoury, M R Rossi, W Harris, C R Flowers, I S Lossos, L H Boise, S S Dave, J Kowalski, L Bernal-Mizrachi
Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28356387/inducible-tap1-negatively-regulates-the-antiviral-innate-immune-response-by-targeting-the-tak1-complex
#16
Zhangchuan Xia, Gang Xu, Xiaodan Yang, Nanfang Peng, Qi Zuo, Shengli Zhu, Hua Hao, Shi Liu, Ying Zhu
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum-associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells...
March 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28337828/tradd-traf2-rip1-and-tak1-are-required-for-tnf-%C3%AE-induced-pro-labour-mediators-in-human-primary-myometrial-cells
#17
Ratana Lim, Gillian Barker, Martha Lappas
PROBLEM: TNF-α plays a central role in the processes of human labour and delivery. This study sought to determine the role of the adaptor proteins TNFR1-associated death domain protein (TRADD), TNF receptor-associated factor 2 (TRAF2), receptor interacting protein 1 (RIP1) and transforming growth factor beta-activated kinase 1 (TAK1) in TNF-α-induced formation of pro-labour mediators. METHOD OF STUDY: Human primary myometrial cells were transfected with siRNA against TRADD (siTRADD), TRAF2 (siTRAF2), RIP1 (siRIP1) or TAK1 (siTAK1), treated with TNF-α, and assayed for pro-inflammatory mediators expression...
March 24, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28323847/role-of-the-mapks-tgf-%C3%AE-1-traf6-signaling-pathway-in-postoperative-atrial-fibrillation
#18
Daoliang Zhang, Xiaoqing Chen, Qian Wang, Shaohui Wu, Yue Zheng, Xu Liu
OBJECTIVES: To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis. METHODS: A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28316375/torilin-inhibits-inflammation-by-limiting-tak1-mediated-map-kinase-and-nf-%C3%AE%C2%BAb-activation
#19
Mehari Endale, Tae-Hwan Kim, Yi-Seong Kwak, Na-Mi Kim, Seung-Hyung Kim, Jae Youl Cho, Bong-Sik Yun, Man-Hee Rhee
Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28301526/novel-copy-number-variation-of-the-tgf%C3%AE-3-gene-is-associated-with-tgf%C3%AE-3-gene-expression-and-duration-of-fertility-traits-in-hens
#20
Lantao Gu, Chenghao Sun, Yangzhang Gong, Mei Yu, Shijun Li
Improvements in the duration of fertility (DF) could increase the interval between successive artificial inseminations, thereby decreasing the cost associated with production of hatching eggs. The molecular mechanisms involved in DF in hens remains under-explored. In this study, expression levels of the transforming growth factor-β genes (TGFβs: TGFβ1, TGFβ2, TGFβ3) were investigated in utero-vaginal junctions (UVJs) of hens with long DF (Group L, n = 10) and short DF (Group S, n = 10). TGFβ1 and 2 tended to exhibit higher expression levels in UVJs from Group L hens...
2017: PloS One
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